The long-term goals of the program are to develop devices capable of protecting a range of hormone-secreting cells in vivo without the need for immunosuppression. The initial focus of the program is development of microfabricated 'biocapsules' composed of highly controlled microarchitectures at physiologically relevant scales (nanometer to micron sizes) for pancreatic islet cells. The 10-30 nm uniform pore sizes allow the exchange of nutrients, waste products, and secreted insulin between host (patient) and implanted cells. This application specifically addresses several key areas for successful development an implantable immunoisolation device containing pancreatic islets for regulation of blood glucose levels in Type 1 diabetes. The following are the specific aims of this proposal: 1) manufacture inorganic biocapsule components at three predetermined pore sizes (12,18, and 24 nm), loading half capsules with porcine islets, and bonding the two halves together; 2) measure insulin release kinetics from biocapsule-encapsulated islet cells from three pore sizes under repeated dynamic conditions until the response is markedly reduced (30 to 40% from initial levels); 3) investigate the effect of two extracellular matrix materials (collagen and Matrigel) on insulin release kinetics and islet survival; and 4) assess cell viability at the end of the in vitro insulin release studies. PROPOSED COMMERCIAL APPLICATIONS: Once successfully developed, this product would be used to treat type-1 diabetics as well as a significant portion of type-2 diabetics. There are about 500,000 type 1 diabetics and nearly ten times as many type-2 diabetics. Thus, a large patient population is available for treatment. The system would need to be replaced at least three to four times a year for the remainder of the patients life.